Perception of odor begins at the olfactory receptor cells present in the olfactory mucosa with receiving odorant molecules suspended in the air by their olfactory receptors. The olfactory receptors, which are a G-protein-coupled receptor, are activated when bound to an odorant molecule and produce cAMP by the mediation of G-protein and adenylate cyclase. Then, cyclic nucleotide-gated (CNG) channel on the olfactory receptor cells are activated by cAMP, and ions influx through the activated channel, whereby the olfactory receptor cells is depolarized. As a result, voltage-dependent channels are opened, and action potentials are generated, to thereby transfer odor-related information to the central nervous system.
Masking of olfaction is accomplished by temporarily inactivating or lessening the aforementioned response and is thought to be more effectively attained when combined with information processing in the central nervous system such as lateral inhibition. Masking of olfaction by fragrance is supposed to affect the affinity of an odor substance to the olfactory mucosa. Some fragrance substances are suggested to have an anesthetic action based on inhibition of enzymatic activity in the olfactory receptor cells (Non-Patent Document 1). However, there has been reported no technique for verifying or objectively evaluating the aforementioned action. Hitherto, such an action must be evaluated through a subjective sensory test in the development of potent olfaction-masking agents.
It is indicated that olfaction is inhibited by inhibiting the information transfer system in the olfactory receptor cells. Actually, some tests employing knockout mice have revealed that olfaction is nullified by lack of signaling molecules: olfactory cell G-protein (Golf) (Non-Patent Document 2), type-III adenylate cyclase (Non-Patent Document 3), and olfactory CNG channel subunit (Non-Patent Document 4). As the olfactory CNG channel is exposed to the olfactory cilia membrane the activity of the CNG channel can be regulated without penetration of an activity-regulating substance through the cell membrane or epithelial cell barrier. Thus, the olfactory CNG channel is an important target to regulate olfaction (Patent Document 1). For example, it has been disclosed that inhibition of the CNG channel by a calcium channel inhibitor reduces olfaction of rats (Patent Document 2). There have been proposed other mechanisms which can be involved in masking of olfaction in the olfactory mucosa, such as a theoretical mechanism employing an antagonist against the olfactory receptor (Non-Patent Document 5) and a theoretical mechanism employing a calcium-dependent potassium channel (Non-Patent Document 6). There have been proposed methods for modulating olfactory sensitivity by inhibition of cAMP-decomposing enzyme in the olfactory cilia (Patent Document 3), controlling the intracellular calcium level (Patent Document 4), and employing an odor-ingredient compound analogue (Patent Document 5).
The voltage-dependent cation channels present on the olfactory receptor cells generate action potential through depolarization of the olfactory receptor cells caused by the CNG channel activity and thus are involved in olfaction transfer. A study has revealed that some odorant molecules inhibit the voltage-dependent cation channels in isolated olfactory receptor cells (Non-Patent Document 7). However, in vivo, most of the voltage-dependent cation channels are present on the cell membranes protected by tight junctions and are not exposed to the olfactory cilia membrane, unlike with the CNG channels. Although various mechanisms as those described above are known to relate to the masking of olfaction, it has not been clearly elucidated whether the voltage-dependent cation channel is involved in olfactory masking.